title: Analysis of the plasma proteome in COPD: Novel low abundance proteins reflect the severity of lung remodeling.
abstract: The search for COPD biomarkers has largely employed a targeted approach that focuses on plasma proteins involved in the systemic inflammatory response and in lung injury and repair. This proof of concept study was designed to test the idea that an open, unbiased, in-depth proteomics approach could identify novel, low abundance plasma proteins i.e., ng/mL concentration, which could serve as potential biomarkers. Differentially expressed proteins were identified in a discovery group with severe COPD (FEV1 <45% predicted; n = 10). Subjects with normal lung function matched for age, sex, ethnicity and smoking history served as controls (n = 10). Pooled plasma from each group was exhaustively immunodepleted of abundant proteins, d separated by 1-D gel electrophoresis and extensively fractionated prior to LC-tandem mass spectroscopy (GeLC-MS). Thirty one differentially expressed proteins were identified in the discovery group including markers of lung defense against oxidant stress, alveolar macrophage activation, and lung tissue injury and repair. Four of the 31 proteins (i.e., GRP78, soluble CD163, IL1AP and MSPT9) were measured in a separate verification group of 80 subjects with varying COPD severity by immunoassay. All 4 were significantly altered in COPD and 2 (GRP78 and soluble CD163) correlated with both FEV1 and the extent of emphysema. In-depth, plasma proteomic analysis identified a group of novel, differentially expressed, low abundance proteins that reflect known pathogenic mechanisms and the severity of lung remodeling in COPD. These proteins may also prove useful as COPD biomarkers.
authors.affiliation: 1Department of Biochemistry, Temple University School of Medicine , Philadelphia, PA , USA.
authors.forename: Salim
authors.initials: S
authors.lastname: Merali
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Barrero
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Diane Er
authors.initials: DE
authors.lastname: Chen
authors.forename: Gerard
authors.initials: G
authors.lastname: Criner
authors.forename: Alan
authors.initials: A
authors.lastname: Braverman
authors.forename: Samuel
authors.initials: S
authors.lastname: Litwin
authors.forename: Anthony
authors.initials: A
authors.lastname: Yeung
authors.forename: Steven G
authors.initials: SG
authors.lastname: Kelsen
mesh_terms: D000368:Aged; D056151:Airway Remodeling; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D000091342:Endoplasmic Reticulum Chaperone BiP; D005541:Forced Expiratory Volume; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000453:epidemiology / Q000473:pathology*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D044465:White People
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human